Strategies to Combat Resistance to Anti-angiogenesis Therapies in Cancer: Current Status and Future Prospects

Abstract: Anti-angiogenic therapy represents a promising approach to cancer treatment by targeting the vascular support systems of tumors rather than the tumor cells themselves. Antiangiogenic agents face numerous obstacles that impede their efficacy, notwithstanding their potential: mechanistic complexity, toxicity, resistance, and the lack of validated predictive biomarkers. Resistance mechanisms may encompass genetic modifications, alternative angiogenic pathways, or the recruitment of cells derived from bone marrow. This work examines present problems and approaches to overcome resistance against anti-angiogenic treatment. Treatment response is predicted by biomarker-guided therapy; patterns of circulating endothelial cells, IL-8 levels, and VEGFR expression indicate possible therapeutic monitoring value. Multi-targeted approaches including drugs that block VEGFR, PDGFR, FGFR, and c-MET concurrently have shown more efficacy than single- pathway inhibition. Additional research indicates that combining treatments has positive results. Combining anti-angiogenic agents with cancer vaccines increases immune responses and tumour regulation. Combining radiotherapy with chemotherapy increases drug delivery and efficacy utilizing vascular normalisation. Techniques based on nanotechnology such as gold nanoparticles and carbon-based materials may enhance medicinal efficacy and delivery. These results reveal that to overcome resistance mechanisms and enhance patient outcomes anti-angiogenic therapy must combine focused therapies with precision medicine approaches.